REFERAT

HERPES ZOSTER
Meiske Dunggio S.Ked ( 13 17 777 14 248)
Laksamana Andika ( 13 17 777 14 238)
Syahrullah Ramadhan ( 13 17 777 14 280)

Supervisor by :
dr. Sukma Anjayani,.Sp.KK.,M.Kes
 HERPES ZOSTER
Herpes Zoster is a self-limiting disease,
characterized by a vesicular dermal eruption distributed
in the region of a cutaneous dermatome, associated or
not with neuropathic pain. It is caused by the reactivation
of the Varicella Zoster Virus (VZV), which remains latent
n the sensory ganglia of the spinal cord after suffering
Varicella as a primary infection.
 EPIDEMIOLOGY
The incidence of herpes zoster is 1.5–3.0 per 1,000
personyears in all ages and 7–11 per 1,000 per year in
persons over 60 years of age in European and North
American studies.13–22 It is estimated that there are
more than a million new cases of herpes zoster in the
United States each year, more than half of which occur
in persons ≥60 years of age, and this number will
increase as the population ages.
 ETIOLOGI AND PATHOGENESIS
The VZV genome encodes about 70 unique genes,
most of which have DNA sequence and functional
homology to genes of the other herpesviruses. Immediate
early (IE) gene products regulate VZV replication. Early
gene products, such as the virus-specific thymidine kinase
and the viral DNA polymerase, support viral replication.
Late genes encode virus structural proteins that serve
as targets for neutralizing antibodies and cellular
immune responses. There is only one VZV serotype.
However, there are multiple VZV genotypes that
display geographic segregation and recombination,
and minor variations in their nucleotide sequences
allow one to distinguish wild type from vaccine virus
strains, and to “fingerprint” viruses isolated from
individual patients.
Entry of VZV is through the mucosa of the upper respiratory
tract and oropharynx. Initial multiplication occurs at this portal
of entry, where VZV infects tonsillar T cells, which disseminate
virus via the blood and lymphatics (the primary viremia).
Infected T cells carry virus to the reticuloendothelial system,
the major site of virus replication during the remainder of the
incubation period, and to the skin, where innate immune
responses delay VZV replication and rash formation.
 During the course of varicella, VZV passes from lesions in the skin
and mucosal surfaces into the contiguous endings of sensory nerves
and is transported centripetally up the sensory fibers to the sensory
ganglia. Infected T cells may also carry virus to sensory gangliah
ematogenously. In the ganglia, the virus establishes a latent infection
that persists for life. Herpes zoster occurs most often in dermatomes in
which the rash of varicella achieves the highest density—those
innervated by the first (ophthalmic) division of the trigeminal nerve and
by spinal sensory ganglia from T1 to L2.
Although the latent virus in the ganglia retains its potential for full
infectivity, reactivation is sporadic and infrequent, and infectious virus
does not appear to be present during latency. The mechanisms involved
in reactivation of latent VZV are unclear, but reactivation has been
associated with immunosuppression; emotional stress; irradiation of the
spinal column; tumor involvement of the cord, dorsal root ganglion, or
adjacent structures; local trauma; surgical manipulation of the spine; and
frontal sinusitis (as a precipitant of ophthalmic zoster). Most important,
though, is the decline in VZV-specific cellular immunity that occurs with
increasing age.
 When VZV-specific cellular immunity falls below some critical
level, reactivated virus can no longer be contained. Virus
multiplies and spreads within the ganglion, causing neuronal
necrosis and intense inflammation, a process that is often
accompanied by severe neuralgia. Infectious VZV then spreads
antidromically down the sensory nerve, causing intense neuritis,
and is released from the sensory nerve endings in the skin, where
it produces the characteristic cluster of zoster vesicles.
 Spread of the ganglionic infection proximally along the
posterior nerve root to the meninges and cord may result in
local leptomeningitis, cerebrospinal fluid pleocytosis, and
segmental myelitis.
 Infection of motor neurons in the anterior horn and
inflammation of the anterior nerve root account for the
local palsies that may accompany the cutaneous
eruption, and extension of infection within the central
nervous system (CNS) may result in rare complications
of herpes zoster (e.g., meningoencephalitis, transverse
myelitis). Viremia also occurs during herpes zoster.
 CLINICAL FINDINGS
Prodrome Of Herpes Zoster
Pain and paresthesia in the involved dermatome often
precede the eruption by several days and vary from superficial
itching, tingling, or burning to severe, deep, boring, or
lancinating pain. The pain may be constant or intermittent and
it is often accompanied by tenderness and hyperesthesia of
the skin in the involved dermatome. The preeruptive pain of
herpes zoster may simulate pleurisy, myocardial infarction,
duodenal ulcer, cholecystitis, biliary or renal colic, appendicitis,
prolapsed intervertebral disk, or early glaucoma, and this may
lead to serious misdiagnosis and misdirected interventions.
 Prodromal pain is uncommon in
immunocompetent persons under 30 years of age,
but it occurs in the majority of persons with herpes
zoster over the age of 60 years. A few patients
experience acute segmental neuralgia without ever
developing a cutaneous eruption—a condition
known as zoster sine herpete.
Rash Of Herpes Zoster

The most distinctive feature of herpes zoster is the

localization and distribution of the rash, which is nearly always
unilateral and is generally limited to the area of skin innervated
by a single sensory ganglion. The area supplied by the
trigeminal nerve, particularly the ophthalmic division, and the
trunk from T3 to L2 are most frequently affected; the thoracic
region alone accounts for more than half of all reported cases,
and lesions rarely occur distal to the elbows or knees.
 Although the individual lesions of herpes zoster
and varicella are indistinguishable, those of herpes
zoster tend to evolve more slowly and usually
consist of closely grouped vesicles on an
erythematous base, rather than the more discrete,
randomly distributed vesicles of varicella.
 Pain Of Herpes Zoster
Although the rash is important, pain is the cardinal
problem posed by A herpes zoster, especially in the
elderly. Most patients experience dermatomal pain or
discomfort during the acute phase (The first 30 days
following rash onset) that ranges from mild to severe.
Patients describe their pain or discomfort as burning,
deep aching, tingling, itching, or stabbing.
 For some patients, the pain intensity is so
great that words like horrible or excruciating are
used to describe the experience. Acute herpes
zoster pain is associated with decreased physical
functioning, emotional distress, and decreased
social functioning.
 Herpes Zoster In The Immunocompromised Host

Except for PHN, most serious complications of herpes

zoster occur in immunocompromised persons. These
complications include necrosis of skin and scarring and
cutaneous dissemination with an incidence as high as 25%–
50%. Patients with cutaneous dissemination also manifest
widespread, often fatal, viscera dissemination, particularly to
the lungs, liver, and brain.
 LABORATORY DIAGNOSIS
The lesions of varicella and herpes zoster are
indistinguishable by histopathology. The presence of
multinucleated giant cells and epithelial cells containing
acidophilic intranuclear inclusion bodies distinguishes
the cutaneous lesions produced by VZV from all other
vesicular eruptions (e.g., those caused by variola and
other poxviruses, and by coxsackieviruses and
echoviruses) except those produced by HSV..
 These cells can be demonstrated in Tzanck
smears prepared at the bedside; material is
scraped from the base of an early vesicle, spread
on a glass slide, fixed in acetone or methanol, and
stained with hematoxylin-eosin, Giemsa,
Papanicolaou, or Paragon multiple stain.
 Punch biopsies provide more reliable material for histologic
examination than Tzanck smears and facilitate diagnosis in the
prevesicular stage and in atypical lesions such as the chronic
verrucous lesions produced by acyclovir-resistant VZV in patients
with AIDS.
 Detection of VZV DNA in clinical specimens following
amplifications by PCR provides the greatest assay
sensitivity, very high specificity and rapid turnaround
time. It has revolutionized the diagnosis of VZV
infections, and can distinguish among wild type and Oka
vaccine strains of VZV and HSV.
 Serologic tests permit the retrospective diagnosis of
varicella and herpes zoster when acute and convalescent
sera are available for comparison. These assays can also
identify susceptible individuals who may be candidates for
isolation or prophylaxis. The technique most commonly used
is a solid-phase enzyme-linked immunosorbent assay
(ELISA). However, this assay often lacks sensitivity and
specificity, failing to detect antibody in people who are
immune and sometimes yielding false-positive results in
susceptible individuals.
 Several more sensitive techniques have been
developed to measure humoral responses to VZV.
These include an immunofluorescence assay for
antibody to VZV-induced membrane antigens
[fluorescent antibody to membrane antigen (FAMA)] that
reliably distinguishes immune from susceptible adults
and a latex agglutination test that is comparable in
sensitivity and specificity to FAMA assays, but is much
simpler to perform.
 TREATMENT
 TOPICAL THERAPY
During the acute phase of herpes zoster, the application of
cool compresses, calamine lotion, cornstarch, or baking soda
may help to alleviate local symptoms and hasten the drying of
vesicular lesions. Occlusive ointments should be avoided, and
creams or lotions containing glucocorticoids should not be used.
Bacterial superinfection of local lesions is uncommon and should
be treated with warm soaks; bacterial cellulitis requires systemic
antibiotic therapy. Topical treatment with antiviral agents is not
effective.
 Anitiviral Treatment
Patient Group Regiment
Normal Symptomatic treatment alone, or Famciclovir 500 mg PO
every 8 h for 7 days or Valacyclovir 1 g PO every 8 h for
Age <50 years 7 days or Acyclovir 800 mg PO 5 times a day for 7 daysa

Age ≥50 years, and patients of Famciclovir 500 mg PO every 8 h for 7 days or
any age with cranial nerve Valacyclovir 1 g PO every 8 h for 7 days of Acyclovir 800
involvement (e.g., ophthalmic
mg PO 5 times a day for 7 daysa
zoster

Immunocompromised Mild Famciclovir 500 mg PO every 8 h for 7–10 days or Valacyclovir

compromise, including HIV-1 1 g PO every 8 h for 7–10 days or Acyclovir 800 mg PO 5 times
infection a day for 7–10 daysa

Severe compromise Acyclovir 10 mg/kg IV every 8 h for 7–10 days

Acyclovir resistant (e.g., Foscarnet 40 mg/kg IV every 8 h until healed
advanced AIDS)
 Anti-Inflammatory Theapy

The possibility that PHN might be caused by

inflammation of the sensory ganglion and
contiguous neural structures provided the rationale
for the use of glucocorticoids during the acute
phase of herpes zoster in an attempt to further
reduce acute pain and prevent PHN.
 Randomized controlled trials, however, showed that the
addition of glucocorticoids to acyclovir did not change the
incidence of chronic pain. However, glucocorticoids did reduce
acute pain in most trials, and in one trial of acyclovir and
prednisone, the time to uninterrupted sleep, return to baseline
daily activity, and cessation of analgesic therapy was reduced in
patients who received glucocorticoids. Consequently, some
experts advocate oral glucocorticoids for otherwise healthy older
adults whose rash is complicated by moderate-to-severe pain and
who have no contraindications to glucocorticoids.
 Others believe that the common adverse effects of
glucocorticoids argue against their routine use in older
patients with herpes zoster. We agree and do not
recommend the use of glucocorticoids in this setting.
Glucocorticoids, in combination with effective antiviral
therapy, may improve motor outcomes and acute pain in
VZV-induced facial paralysis and cranial polyneuritis,
where compression of affected nerves may contribute to
disability.
 Analgesics
Greater severity of acute pain is a risk factor for
PHN, and acute pain may contribute to central
sensitization and the genesis of chronic pain. Therefore,
aggressive pain control is both reasonable and humane.
The severity of acute herpes zoster pain should be
determined using simple standardized pain scales.
 Clinicians should prescribe nonopiate or opiate
analgesics with the goal of limiting the severity of pain to less
than 3 or 4 on a 0-to-10 scale, and to a level that does not
interfere with sleep. The choice, dosage, and schedule of
drugs are governed by the patient’s pain severity, underlying
conditions, and response to specific drugs.
TREATMENT OF POST HERPETIC NEURALGIA
 Topical Therapy
Topical anesthesia delivered by means of a 5% lidocaine patch has been
shown in controlled clinical trials to produce significant pain relief in patients
with PHN. The 10 × 14-cm lidocaine patch contains 5% lidocaine base,
adhesive, and other ingredients on a polyester backing. It is easy to use and is
not associated with systemic lidocaine toxicity. Up to three patches are applied
over the affected area for 12 hours a day. The disadvantages of the patch are
application site reactions, such as skin redness or rash, and substantial cost.
Eutectic mixture of local anesthetics (EMLA) cream applied once a day over the
affected area under an occlusive dressing is an alternative method of delivering
topical anesthesia.
 Oral Agents
Gabapentin has been shown to produce moderate or greater pain
relief in 41%–43% of patients with PHN compared to 12%–23% in
patients receiving placebo. Frequent adverse effects of gabapentin
include somnolence, dizziness, and peripheral edema. Pregabalin has
been shown to produce 50% or greater pain relief in 50% of patients
with PHN compared to 20% in placebo recipients. Dizziness,
somnolence, and peripheral edema were also the most common
adverse effects reported for pregabalin. Pregabalin has a less
complicated dose titration schedule and a faster onset of action than
gabapentin.
 COMPLICATIONS
Cutaneous Visceral Neurologic

Bacterial superinfection Pneumonitis - Post herpetic neuralgia

Scarring hepatitis - Meningoencepalitis
zoster gangrenosum esopahagitis - Myelitis tranverase
Cutaneous dissemination gastritis - Peripheral nerve palsies
pericarditis - motor
cystitis - autonomic
Arthritis -Cranial nerve palsies
- Sensory loss
  - Deafness
- Ocular complications
-Granulomatous angiitis
(causing contralateral
hemiparesis)
DIFERENTIAL DIAGNOSIS
Most Likely Consider Always Rule Out

Zosteriform herpes Papular urticaria Bullous pemphigoid

simplex

Contact dermatitis Erythema multiforme Pemphigus vulgaris

Insect bites Drug eruptions Dermatitis

herpetiformis

Burn Scabies Epidermolysis bullosa

 ZOSTER VACCINE
Until universal varicella vaccination greatly reduces the
number of people latently infected with wild-type VZV, prevention
of herpes zoster must be aimed at preventing reactivation and
spread of the latent wild-type VZV. Long-term suppressive
acyclovir treatment is only practical in immunocompromised
patients at proven risk of developing herpes zoster within a
defined time period, for example, in the year following bone
marrow or solid organ transplantation. Other strategies must be
devised for the general population.
 The zoster vaccine may be administered without screening for
a history of varicella or herpes zoster, nor should one conduct
serologic testing for varicella immunity before vaccination.
Persons known to be VZV seronegative should be vaccinated
against varicella according to current recommendations. Older
adults who have PHN or who have a current episode of herpes
zoster may ask to be vaccinated, but zoster vaccination is not
indicated to treat acute herpes zoster or PHN.
 Some patients may want to receive zoster vaccine
after a recent episode of herpes zoster has resolved.
The optimal time to immunize an individual after a recent
episode of herpes zoster is unknown, and the clinical
diagnosis of herpes zoster is not always correct. The
authors believe that an interval of 3–5 years after the
onset of a well-documented case of herpes zoster is
reasonable.